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  • Title: Effects of disease, route of administration, cigarette smoking, food intake on the pharmacokinetics and circulatory effects of isosorbide dinitrate.
    Author: Fung HL, Ruggirello D, Stone JA, Parker JO.
    Journal: Z Kardiol; 1983; 72 Suppl 3():5-10. PubMed ID: 6666234.
    Abstract:
    The major goal of this study was to examine the clinical pharmacology of isosorbide dinitrate (ISDN) under various conditions of clinical use. Orally administered ISDN is subjected to extensive metabolism during its first passage through the liver. It is not known, however, whether the systemic availability and the circulatory effects of oral ISDN might be affected in clinical conditions under which hepatic blood flow and/or metabolic activity might have been altered. Sublingual (5 mg) and oral (30 mg) ISDN were given under fasting conditions on two separate occasions to (a) patients with angina pectoris (AP), n = 8; (b) patients with chronic congestive heart failure (CHF), n = 9; (c) smoking AP patients, n = 7; and (d) nonsmoking AP patients, n = 9. Patients in group (a) were also given oral ISDN after a standard breakfast. Circulatory effects, i.e., heart rate, systolic and diastolic pressures were measured over 3 h after sublingual dosing and 6 h after oral dosing in both the supine and standing positions. Plasma ISDN concentrations were measured by gas chromatography over the same periods. The systemic availability of oral ISDN was found to be about half that of sublingual ISDN, but the intersubject variability was large. Thus some individuals absorbed oral ISDN as well as they did sublingual ISDN, while others only absorbed oral ISDN minimally. The extent of oral ISDN absorption was not statistically different between patients with AP and CHF, between smokers and nonsmokers, or between the fasting and postprandial conditions, although there was a trend for higher plasma ISDN concentrations in smokers. Food reduced the apparent absorption rate of oral ISDN.(ABSTRACT TRUNCATED AT 250 WORDS)
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